ArticleProceedings of the National Academy of Sciences of the United States of America2014
Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 87 citations in OpenAlex.
- Gut microbiota in chronic inflammation: the interplay with lipid mediators.Gut microbes · 2026Review
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- Betanin ameliorates dextran sulfate sodium-induced colitis in mice by modulating tight junction protein expression.Biochemistry and biophysics reports · 2026Article
- Experimental Research Progress of mPGES-1 Inhibitor 2,5- dimethylcelecoxib in Various Diseases.Current medicinal chemistry · 2026Review
- Stromal cells in normal colon and colon cancers: importance of thyroid hormone signaling.Cell death & disease · 2025Review
- IL-1R2 promotes tumorigenesis and modulates the tumor immune microenvironment in colorectal cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Article
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Regulation of intestinal epithelial homeostasis by mesenchymal cells.Inflammation and regeneration · 2024Review
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- Colitis-associated carcinogenesis: crosstalk between tumors, immune cells and gut microbiota.Cell & bioscience · 2023Review
- The Role of Lipids in the Regulation of Immune Responses.Nutrients · 2023Review
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- Loss of primary cilia promotes inflammation and carcinogenesis.EMBO reports · 2022Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Investigating local and systemic intestinal signalling in health and disease with Drosophila.Disease models & mechanisms · 2022Review
- TPL-2 Inhibits IFN-β Expression via an ERK1/2-TCF-FOS Axis in TLR4-Stimulated Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- NF-κB Inducing Kinase Regulates Intestinal Immunity and Homeostasis.Frontiers in immunology · 2022Review
- Essential immune functions of fibroblasts in innate host defense.Frontiers in immunology · 2022Review
- Fibroblasts in intestinal homeostasis, damage, and repair.Frontiers in immunology · 2022Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 5 institutions in 5 countries.
Funding
Abstract
Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)-prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.